New Publication and the Dream of Predicting Immunotherapy Response in Lung Cancer

Updated: Apr 4

8 May 2017

Dear Friends,

I am pleased to announce that our recent publication “Cellular Expression of PD-L1 in Peripheral Blood of Lung Cancer Patients is Associated with Worse Survival” has been accepted for publication in Cancer Epidemiology Biomarkers & Prevention and is now available online, open access.

In this study, we recruited blood from patients about to receive biopsy to confirm lung cancer. We looked for rare cell populations in the blood, and found a subpopulation of cells with malignant morphometrics (i.e. nuclear morphology) that expressed PD-L1, but not blood-lineage CD45 or epithelial-lineage cytokeratins! These cells were very rare in patients without cancer, and for those with cancer, higher levels of them before treatment was associated with poor overall survival.

PD-L1 is an important emerging biomarker with much promise to predict patient response to what was up until recently the black swan of oncology: immunotherapy. MIT Technology Review recently produced a fantastic overview.

Immunotherapy, as the name suggests, removes checkpoints in the patient’s immune system to recognize their cancer as foreign. When this happens, tumors can almost literally melt away from patients. But, there is a catch: depending on the indication, only 10-20% of patients see benefit from these new drugs, and the rest continue to see their cancer progress, making it more difficult to treat. But, the patients for whom it works generally have very long, sustained responses, some have even been declared “cured,” a word seldom used to describe someone who previously had advanced, metastasized cancer. The biology surrounding the interactions of the immune system and tumors are bewilderingly complex, and there is unfortunately much basic biology that remains unknown, especially why some patients respond resoundingly well to immunotherapies and some do not. But, there is one biomarker that when present on tumor cells can sometimes predict these responses: a protein called PD-L1.

Current means to measure PD-L1 protein on lung tumor cells still requires a lung biopsy, where a large needle has to transverse healthy tissue and puncture the thoracic cavity, potentially causing complications like collapsed lung. There is a tremendous unmet medical need to predict immunotherapy response without biopsy. The patients in our study did not go on to immunotherapy agents, so it’s not possible to tell if these rare cells are predictive of response to immunotherapy agents. However, a follow-up study will be investigating the response to immunotherapy agents in relation to pre-therapy detection of these rare cells.